First clinical trial shows safety and effectiveness of CAR T therapy for prostate cancer
Last reviewed: 14.06.2024
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Treatment of prostate cancer with immunotherapy is currently difficult to implement. However, results from the world's first phase 1 clinical trial using chimeric antigen receptor (CAR) T-cell therapy developed by researchers at the City of Hope, one of the largest cancer research and treatment organizations in the United States, showed that patients with;prostate cancer can be safely treated with cell-based immunotherapy with promising therapeutic activity, according to a phase 1 study published today in Nature Medicine.
The study treated 14 patients with metastatic castration-resistant prostate cancer (mCRPC) who were diagnosed with prostate stem cell antigen (PSCA), which spreads beyond the prostate and fails to respond to hormonal treatment, using T therapy -cells with CAR. More than 34,000 men with this type of prostate cancer die each year in the United States.
Saul Priceman, Ph.D., assistant professor at City of Hope, Department of Hematology and Hematopoietic Cell Transplantation, and colleagues developed CAR T cells targeting prostate stem cell antigen (PSCA), identified as highly expressed in prostate cancer patients. The treatment took the patient's immune cells - called T cells - from the bloodstream and reprogrammed them in the laboratory with CARs to recognize and attack the PSCA protein on the surface of cancer cells. The CAR T cells were then injected back into the patient's body to kill cancer cells.
Prostate cancer has been called an immune desert - a nebulous tumor difficult to treat with immunotherapies because many T cells do not get inside the tumor. It takes something really powerful to overcome this. Our study shows that City of Hope's CAR T-cell therapy for prostate cancer may be a step toward achieving this goal."
Tanya Dorff, PhD, Division Director of the City of Hope Genitourinary Diseases Program and Professor in the Department of Medical Oncology and Therapeutic Research
“The main finding of our study is that PSCA CAR T cells targeted are safe and effective against mCRPC,” Priceman added. "This opens up the possibility of further developing this type of cellular immunotherapy for these patients who currently have no other effective treatment options."
The objectives of the trial were to examine treatment safety and dose-limiting toxicity, as well as preliminary data on treatment efficacy in patients.
The study's outcome: Patients received a single infusion of 100 million CAR T cells without prior lymphodepletion chemotherapy, which is routinely used to treat blood disorders to boost the effectiveness of CAR T cell treatments. Because this was the first-ever clinical trial of CAR T cells, it was important to evaluate the safety of CAR T cells alone in patients. With the same dose of CAR T cells and lymphodepletion, a dose-limiting toxicity complication of cystitis, or bladder irritation, occurred. Dorff explained that PSCA is also present in the bladder, so the CAR T cells likely attacked bladder cells, causing inflammation. The researchers then added a new group to the study with reduced lymphodepletion, which mitigated this toxicity. Four of the 14 patients experienced a decrease in PSA levels, a serial marker of disease progression in prostate cancer patients, including one patient with a significant decrease. The images showed treatment responses in a subset of treated patients. Five of the 14 patients had mild to moderate cytokine release syndrome, which can be caused by a large, rapid release of cytokines into the blood from immune cells and is a common side effect after CAR T-cell treatment. CRS is a treatable side effect. CAR T cells did not persist at high levels beyond the 28-day observation period, limiting the effectiveness of the treatment. This represents a common problem in the field of CAR T cells for treating solid tumors, which the researchers plan to address in a follow-up study in City of Hope using a therapy that is now available for enrollment. One patient, who had already undergone several previous therapies, responded favorably to CAR T-cell therapy. His PSA levels dropped by 95%, and the cancer in his bones and soft tissue also shrank. He experienced this positive response for approximately eight months.
"The patient's results were very encouraging, and we are deeply grateful for his participation in our study, as well as the other patients and their families," Dorff said. "We want to continue with this therapy and increase the number of CAR T cells and continue to closely monitor any health issues, as we believe this may improve the effectiveness of the treatment."
A Phase 1b clinical trial using PSCA CAR T cell therapy combined with radiation therapy to enhance anti-tumor activity aims to enroll up to 24 patients.
City of Hope, a recognized leader in the field of CAR T-cell therapy, has treated nearly 1,500 patients since initiating its CAR T-cell therapy program in the late 1990s. The institution continues to have one of the most extensive CAR T-cell therapy clinical research programs in the world, with approximately 70 CAR T-cell clinical trials currently underway, including 13 different solid tumor types. The studies use City of Hope-developed therapies and industry products. A recent study published in Nature Medicine introduced City of Hope's CAR T cell therapy for brain tumors.